The possibility exists that abnormalities in apolipoprotein metabolism may play an etiological role in one or more of the hyperlipoproteinemias. The present study is concerned with evaluating the mechanism of catabolism and the catabolic site(s) of one of the major apolipoproteins, using a laboratory animal model. Our approach in this study is based on the concept that the plasma lipoprotein system consists of families of lipoproteins (e.g. lipoprotein A, lipoprotein B and lipoprotein C), each of which is characterized by a distinct protein moiety (e.g. apolipoprotein A, apolipoprotein B and apolipoprotein C, respectively) representing unique chemical and biochemical characteristics of each family. Our proposal focuses on apolipoprotein A (Apo A) metabolism. We now have extensive experience with solubilization, purification and I125 labeling of Apo A-I. Our initial studies utilized the dog as an ideal model because of its high concentrations of Apo A and the lipoprotein A family as major cholesterol carrier in plasma. Our published or in press studies have reported on canine turnover kinetics, specific organ site(s) of catabolism and specific subcellular site of catabolism of Apo A-I or HDL3, and on isolated rat liver parenchymal cell binding, uptake and proteolytic degradation of HDL3. We have begun a series of studies on apolipoprotein catabolism by rat liver parenchymal cells in culture. BIBLIOGRAPHIC REFERENCE: Nakai T, Otto PS and Whayne TF Jr: Canine apolipoprotein degradation by acid proteases in canine liver lysosomes. Circulation 52, Suppl. II: 40, 1975 (Abstract) (Presented). Nakai T, Otto PS and Whayne TF Jr: Proteolysis of canine apolipoprotein by acid proteases in canine liver lysosomes. Biochim Biophys Acta 422: 380, 1976.